Characterization of CCK-B/gastrin-like receptors in human gastric carcinoma.
In this study we identified and characterized the receptor related to the modulation of growth of human gastric cancer by gastrin. By performing receptor binding assays on human AGS gastric cancer cells with the selective CCK-B/gastrin receptor antagonist [3H]L-365,260, specific and saturable binding were determined. Binding was dependent on protein concentration, time, temperature, and the presence of protease inhibitors, and was located in the membrane fraction. Gastrin, as well as CCK, stimulated gastric cancer cell growth in a receptor-mediated fashion at a concentration consistent with the binding affinity. Receptor gene expression for the CCK-B/gastrin receptor, but not for the CCK-A receptor, was found by reverse transcription polymerase chain reaction. Receptor binding assays as well as transcriptional and growth studies provide evidence that gastrin-stimulated growth of human gastric cancer is mediated by CCK-B/gastrin-like receptors.
Smith
J P
JP
Division of Gastroenterology, The Milton S. Hershey Medical Center, The Pennsylvania State University, 500 University Drive, Hershey, PA, 17033-0850, USA.
Shih
A H
AH
Wotring
M G
MG
McLaughlin
P J
PJ
Zagon
I S
IS
D001570:Benzodiazepinones / Q000378:metabolism*; D002766:Cholecystokinin / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005755:Gastrins / Q000494:pharmacology*; D015870:Gene Expression; D006133:Growth Substances; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010671:Phenylurea Compounds / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects
D001570:Benzodiazepinones; D005755:Gastrins; D006133:Growth Substances; D010671:Phenylurea Compounds; D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002766:Cholecystokinin